Major structural issues like foundation damage, electrical concerns with exposed wires or unsafe wiring, plumbing perils such as leaky pipes or mold growth, HVAC problems with uneven heating or poor air quality, and potential hidden issues like asbestos or radon gas are critical home inspection red flags that can impact safety, health, and property value. Addressing these concerns promptly through regular maintenance or seeking professional help is crucial to maintain a safe, comfortable, and valuable home.